NIH study suggests that early detection is possible for prion diseases

A fast test to diagnose fatal brain conditions such as mad cow disease
in cattle and Creutzfeldt-Jakob disease in humans could be on the horizon,
according to a new study from National Institutes of Health scientists.
Researchers at NIH's
National Institute of Allergy and Infectious Diseases (NIAID) have developed
a highly sensitive and rapid new method to detect and measure infectious agents
called prions that cause these diseases.

"Although relatively rare in humans and other animals, prion diseases are devastating
to those infected and can have huge economic impacts," says Anthony S. Fauci,
M.D., director of NIAID. "Scientists have promising concepts for developing therapies
for people infected with prion diseases, but treatments are helpful only if it
is known who needs them. This detection model could eventually bridge that gap."

Prion diseases are primarily brain-damaging conditions also known as transmissible
spongiform encephalopathies. They are difficult to diagnose, untreatable and
ultimately fatal. A key physical characteristic of these diseases is dead tissue
that leaves sponge-like holes in the brain. Prion diseases include mad cow disease,
or bovine spongiform encephalopathy in cattle; scrapie in sheep; Creutzfeldt-Jakob
disease in humans; and chronic wasting disease in deer, elk and moose. For more
information about NIAID research on prion diseases, visit the NIAID Prion Diseases
portal (http://www.niaid.nih.gov/topics/prion/Pages/default.aspx).

Currently
available diagnostic tests lack the sensitivity, speed or quantitative capabilities
required for many important applications in medicine, agriculture, wildlife biology
and research. Because prion infections can be present for decades before disease
symptoms appear, a better test might create the possibility for early treatment
to stop the spread of disease and prevent death.

Now, a blending of previous
test concepts by the NIAID group has led to the development of a new prion detection
method, called real time quaking induced conversion assay, or RT-QuIC. This approach
is described in a paper now online in the open-access journal PLoS Pathogens.
Byron Caughey, Ph.D., led the study at NIAID's Rocky Mountain Laboratories in
Hamilton, Mont.

Scientists believe disease-causing prions are abnormal infectious
clusters of prion protein molecules. Normally, prion protein molecules are unclustered,
harmless and found in every mammal. In a process not fully understood, abnormal
infectious clusters develop and can convert normal prion protein molecules into
the infectious prion form; these clusters tend to gather in the brain. Ongoing
replication allows the disease to spread and damage the brain.

Infectious prions
also are found outside the brain, in saliva, blood, breast milk, urine and the
nasal and cerebral spinal fluids used in the study. But the concentrations of
infectious prions in these bodily fluids are so low that scientists, clinicians
and wildlife biologists have not been able to measure them for routine purposes.

The new assay can detect when miniscule amounts of infectious prions initiate
the conversion of large amounts of normal prion protein into an abnormal form
in test-tube reactions. By comparing the extent to which different samples can
be diluted and still initiate conversion, scientists can estimate the relative
infectious concentrations in the original samples. In their study, the NIAID
scientists used RT-QuIC to detect prion infections in deer known to have chronic
wasting disease and sheep known to have scrapie. In scrapie-infected hamsters,
they found surprisingly high levels of prions in nasal fluids, pointing to such
fluids as possible sources of contagion in various prion diseases.

Along with
optimizing their existing applications in the laboratory, Dr. Caughey and his
colleagues are teaming up with a number of other laboratories around the world
to extend the practical and scientific applications of RT-QuIC. Related testing
approaches might also aid the diagnoses of similar neurodegenerative protein
diseases, such as Alzheimer's, Huntington's and Parkinson's diseases.

NIAID conducts and supports research — at NIH, throughout the United States, and
worldwide — to study the causes of infectious and immune-mediated diseases, and
to develop better means of preventing, diagnosing and treating these illnesses.
News releases, fact sheets and other NIAID-related materials are available on
the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services. NIH
is the primary federal agency conducting and supporting basic, clinical, and
translational medical research, and is investigating the causes, treatments,
and cures for both common and rare diseases. For more information about NIH
and its programs, visit http://www.nih.gov.